2GE2

Solution structure of the Duplex DNA Containing the 3-(Deoxyguanosin-N2-yl)-2-Acetoaminofluorene

Summary for 2GE2

• Entry DOI: 10.2210/pdb2ge2/pdb
• Descriptor: 5'-D(*CP*GP*TP*AP*CP*GP*CP*AP*TP*GP*C)-3', 5'-D(*GP*CP*AP*TP*GP*CP*GP*TP*AP*CP*G)-3', 2-ACETYLAMINOFLUORENE-3-YL (3 entities in total)
• Functional Keywords: dna, acetylaminofluoren (aaf)
• Total number of polymer chains: 2
• Total formula weight: 6931.67

Authors

de los Santos, C.,Zaliznyak, T. (deposition date: 2006-03-17, release date: 2006-07-04, Last modification date: 2024-05-29)

Primary citation

Zaliznyak, T.,Bonala, R.,Johnson, F.,de Los Santos, C.
Structure and Stability of Duplex DNA Containing the 3-(Deoxyguanosin-N(2)-yl)-2-acetylaminofluorene (dG(N(2))-AAF) Lesion: A Bulky Adduct that Persists in Cellular DNA.
Chem.Res.Toxicol., 19:745-752, 2006

PubMed Abstract: The carcinogenic environmental pollutant 2-nitrofluorene produces several DNA adducts including the minor 3-(deoxyguanosin-N(2)-yl)-2-acetylaminofluorene (dG(N(2))-AAF) lesion, which persists for long times in rat tissue DNA after discontinuation of carcinogen administration. Here, we present the solution structure of a dG(N(2))-AAF duplex as determined by NMR spectroscopy and restrained molecular dynamics. The data establish a regular right-handed conformation with Watson-Crick base pair alignments throughout the duplex. The AAF moiety resides in the minor grove of the helix with its long axis directed toward the 5'-end of the modified strand. Restrained molecular dynamics shows that the duplex structure adjusts to the AAF lesion, reducing its exposure to water molecules. Analysis of UV melting profiles shows that the presence of dG(N(2))-AAF increases the thermal and thermodynamic stability of duplex DNA, an effect that is driven by a favorable entropy. The structure and stability of the dG(N(2))-AAF duplex have important implications in understanding the recognition of bulky lesions by the DNA repair system.

PubMed: 16780352
DOI: 10.1021/tx060002i

Experimental method

SOLUTION NMR